Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

A Phase 2a Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

Background:

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system caused by a mutation in the FAS gene. In ALPS, the body stores too many germ-fighting cells called lymphocytes. This can lead to an enlarged spleen and lymph nodes. Current treatments for ALPS can have many adverse effects. Better treatments for ALPS are needed.

Objective:

To test a study drug (soquelitinib) in people with ALPS.

Eligibility:

People aged 16 years and older with ALPS.

Design:

Participants will have 8 clinic visits and 6 remote visits within 1 year.

Participants will be screened. They will have a physical exam with blood and urine tests. Some may have tests of their lung function.

Soquelitinib is a tablet taken by mouth twice a day. Participants will record their doses and any symptoms on a paper or online form.

Blood tests and other procedures will be repeated during study visits. Three visits will include imaging scans. Participants will lie on a table that slides through a doughnut-shaped machine while X-rays capture pictures of the inside of their body.

Some participants may be able to remain in the study for a second year....

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Lymphoproliferative Syndrome
• Intervention / Treatment: Drug: Soquelitinib

Detailed Description

Study Description:

This is a multisite open-label phase 2a study to evaluate the safety, tolerability, and preliminary efficacy of the interleukin (IL)-2 inducible T-cell kinase (ITK) inhibitor soquelitinib for treating ALPS-FAS. This study will be conducted in two stages. In the first stage, following a background drug washout of up to 90 days, 8 participants will receive 200 mg of soquelitinib twice daily for up to 360 days, with approximately monthly study visits (in person or remote). A safety and futility interim analysis will be conducted after all 8 participants have had a computed tomography (CT) or positron emission tomography (PET)/CT scan at day 90 and have completed at least 80% of their study drug regimen. If at least one participant has a positive response to the study drug and there are no safety concerns among the 8 participants, then the study will proceed to stage 2, in which 6 new participants will be enrolled and, following a background drug washout of up to 90 days, receive the same dosage as stage 1 (200 mg twice daily for 360 days). Individual participation concludes at the end of the 360-day regimen.

Participants may re-enroll once in the study. They will repeat the whole study schedule except for the screening visit, but they will have a study drug washout period of up to 90 days with monthly visits during that time. Upon reaching pre-specified criteria, they will begin a second 360-day regimen of soquelitinib at 200 mg twice daily.

The primary endpoints will be assessed after all 6 participants of stage 2 have had a CT or PET/CT scan at day 90 and have completed at least 80% of their study drug regimen. The trial will automatically be determined a failure if safety concerns or lack of positive response prevent progression to stage 2.

Primary Objectives:

To determine the efficacy of soquelitinib in reducing spleen volume or target lymph node volume in people with ALPS-FAS.

Secondary Objective:

1. To determine the efficacy of soquelitinib in improvement of lymphoproliferation and autoimmune disease, including cytopenias, in

   people with ALPS-FAS.

2. To determine the safety and tolerability of soquelitinib in people with ALPS-FAS.

Primary Endpoints:

Reduction of spleen volume or target lymph node volume by 25% from baseline to day 90, assessed by CT or PET/CT scan.

Secondary Endpoints:

1. Shrinkage in spleen volume from baseline to day 90.
2. Shrinkage in target lymph node volume from baseline to day 90.
3. Reduction of cytopenias by one severity level from baseline to day 90.
4. Reduction in prednisone dosage.
5. Grade 3 or 4 systemic infections within 360 days (first or second regimen).
6. Clinically significant worsening of viral, mycobacterial, or fungal infection requiring new treatment or change of treatment by day 360 (first or second regimen).
7. Any drug-related grade 3 or 4 adverse event (AE) that triggers a pause.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: V. Koneti Rao, M.D.; Phone Number: (301) 496-6502; Email: kr191c@nih.gov
• Study Contact Backup: Name: Alanvin D Orpia, R.N.; Phone Number: (240) 550-3663; Email: alanvin.orpia@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: Alanvin Orpia, B.S.N.; Phone Number: 240-669-2935; Email: alanvin.orpia@nih.gov
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • The Children's Hospital of Philadelphia
      • Contact: David Teachey; Phone Number: 267-426-5802; Email: teacheyd@chop.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Texas Children's Hospital
      • Contact: Carl Allen; Phone Number: 832-824-4312; Email: ceallen@txch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

To be eligible to participate in this study and to re-enroll, an individual must meet all the following criteria:

1. Aged >= 16 years.
2. Able to provide informed consent (for ages >= 18 years) or has a parent(s) or guardian(s) who can provide permission to participate on their behalf (for ages <18 years).
3. Has a documented diagnosis of ALPS-FAS.
4. Has clinical evidence of active disease, defined as at least one enlarged lymph node and/or enlarged spleen.
5. If currently on corticosteroid therapy, then dose is less than 20 mg/day (prednisone equivalent) and has been stable for at least 4 weeks.
6. For participants to be seen at the NIH CC, co-enrolled on NIH protocol 93-I-0063.
7. Participants who can become pregnant or who can impregnate their partner must agree to either remain sexually abstinent or use two highly effective methods of contraception when engaging in sexual activities that can result in pregnancy, beginning 28 days before baseline until 3 months after the last dose. One method must be a barrier (eg, internal or external condom, cervical cap, or diaphragm). The second method may be any of the following:

7a. Oral contraceptive pill or hormonal patch or ring.

7b. Parenteral hormonal contraceptive implant.

7c. Intrauterine device.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation or re-enrollment in this study:

1. Profound grade 3 or 4 cytopenias that cannot be improved with immunomodulatory treatments prior to enrolling in the clinical trial and starting the study drug. Per investigator discretion, individuals on a single agent may be included if the dose is stable for 12 weeks at screening and is not expected to confer additive toxicity.
2. Renal impairment, defined as serum creatinine >1.5 mg/dL (or 133 micromol/L) or estimated glomerular filtration rate <60 mL/min/1.73 m^2.
3. Liver impairment, defined as bilirubin, alanine aminotransferase, or aspartate aminotransferase greater than 2.5 times the upper limit of normal.
4. History of EBV-associated lymphoma.
5. Active EBV infection with EBV load >300 copies/mL.
6. Tuberculosis infection (active or latent) or undergoing tuberculosis treatment.
7. Infection with HIV or hepatitis B or C.
8. Current other invasive or systemic fungal, bacterial, or viral infection requiring therapy.
9. History of opportunistic infection within the previous 180 days.
10. History of invasive malignancy that required systemic therapy within the last 3 years.
11. Current use of moderate or strong cytochrome P450 isozyme (CYP)3A inhibitors or inducers that cannot be stopped before day 0.
12. Current use of P-glycoprotein (P-gp) inhibitors that cannot be stopped before day 0.
13. Known hypersensitivity or contraindication to CT contrast agent.
14. Pregnant or breastfeeding.
15. Any condition that, in the opinion of the study team contraindicates participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; The initial dosage for stage 1 of this study is 200 mg twice daily for up to 360 days. If stage 1 is repeated because there are no successes at this dosage, then it will be increased to 400 mg twice daily for up to 360 days. Alternatively, if there are safety concerns at either dosage, then it will be decreased to 100 mg twice daily for up to 360 days.	Drug: Soquelitinib; Soquelitinib is an ITK inhibitor in clinical development for treating relapsed/refractory T-cell lymphoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of spleen volume or target lymph node volume by 25% from baseline to day 90, assessed by CT or PET/CT scan.	To determine the efficacy of soquelitinib in reducing spleen volume or target lymph node volume in people with ALPS-FAS.	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shrinkage in spleen volume from baseline to day 90.	To determine the efficacy of soquelitinib in improvement in lymphoproliferation and autoimmune disease, including cytopenias, in people with ALPS-FAS.	Day 90
Shrinkage in target lymph node volume from baseline to day 90.	To determine the efficacy of soquelitinib in improvement in lymphoproliferation and autoimmune disease, including cytopenias, in people with ALPS-FAS.	Day 90
Reduction of cytopenias by one severity level from baseline to day 90	To determine the efficacy of soquelitinib in improvement in lymphoproliferation and autoimmune disease, including cytopenias, in people with ALPS-FAS and to determine the safety and tolerability of soquelitinib in people with ALPS-FAS.	Day 90
Reduction in prednisone dosage.	To determine the efficacy of soquelitinib in improvement in lymphoproliferation and autoimmune disease, including cytopenias, in people with ALPS-FAS	End of Study
Grade 3 or 4 systemic infections within 360 days.	To determine the safety and tolerability of soquelitinib in people with ALPS-FAS.	Day 360
Clinically significant worsening of viral, mycobacterial, or fungal infection requiring new treatment or change of treatment by day 360.	To determine the safety and tolerability of soquelitinib in people with ALPS-FAS.	End of Study
Any drug-related grade 3 or 4 AE AE that triggers a pause.	To determine the safety and tolerability of soquelitinib in people with ALPS-FAS.	End of Study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: V. Koneti Rao, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• Price S, Shaw PA, Seitz A, Joshi G, Davis J, Niemela JE, Perkins K, Hornung RL, Folio L, Rosenberg PS, Puck JM, Hsu AP, Lo B, Pittaluga S, Jaffe ES, Fleisher TA, Rao VK, Lenardo MJ. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014 Mar 27;123(13):1989-99. doi: 10.1182/blood-2013-10-535393. Epub 2014 Jan 7.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 11, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: November 28, 2025

More Information

Terms related to this study

• Keywords: Lymphoproliferation; Fas; Hypersplenism; Autoimmune Lymphoproliferative Syndrome; Interleukin-2 Inducible T-cell Kinase; Soquelitinib; Targeted Treatment
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Splenic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Autoimmune Lymphoproliferative Syndrome; Autoimmune Lymphoproliferative Syndrome, Type IA; Hypersplenism
• Other Study ID Numbers: 10001824; 001824-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Clinical, laboratory, imaging and demographic data.
• IPD Sharing Time Frame: Following interim review and/or completion of study.
• IPD Sharing Access Criteria: Requests are reviewed by PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No